The zona pellucida of the mammalian oocyte plays a major role in sperm-egg recognition and prevention of polyspermy. Consequently, antibodies prepared against zona antigens could serve as antifertility agents. To test this hypothesis cynomolgus monkeys were directly immunized with heat-solubilized porcine zonae pellucidae. To assess the levels of antibody titers a rapid solid-phase radioimmunoassay was employed utilizing 125-I-protein A. Six weeks after initial immunization a high titer of serum antibody was exhibited. Conceptions occurred up to ten weeks after initial immunization. Further conceptions could occur only 9-20 months following last immunization in 4 monkeys. Two of these fetuses were still-born. The results indicated that the circulating antibodies were unable to reach oocytes in large antral follicles or those in the fallopian tube. Instead, the antibody matrix effected oocytes of developing follicles. This was supported by the observation of massive (as high as 50%) atresia among growing oocytes in ovaries removed 18 months after initial immunization. Nevertheless, infertility was reversible in some of these monkeys. Other aspects of zona function in the fertilization process are being studied in the murine system. Experiments are in progress to determine whether a physiological change referred to as zona hardening, has any relationship to block to polyspermy. In vitro fertilization and zona solubilization procedures are being employed in this project.